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Novel DOCK8 gene mutations lead to absence of protein expression in patients with hyper-IgE syndrome

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Abstract

Autosomal recessive hyper-immunoglobulin E syndrome (AR-HIES) caused by DOCK8 defects is characterized by recurrent elevated serum IgE level, elevated peripheral eosinophil count, severe atopy, recurrent viral and bacterial infections, and early-onset malignancy. The clinical, genetic, and immunologic characteristics of DOCK8 mutations in Chinese patients have not been characterized in detail. In this research, we screened seven Chinese candidate patients for mutations within the DOCK8 gene and identified three large novel homozygous deletions and four novel point mutations by targeted deep sequencing. The homozygous deletions displayed autosomal recessive inheritance, and the point mutations were sporadic. Absence of DOCK8 protein was confirmed using flow cytometry and western blotting. Besides the typical clinical features and immunologic impairments of DIDS, proliferation of lymphocytes, cytotoxic function of NK cells, and expression of IL-10 in regulatory B cells were severely impaired in DOCK8 mutant patients which may be associated with abnormal immune responses in DIDS. These findings will contribute to the early diagnosis and treatment of DOCK8 patients.

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Acknowledgments

We thank all the participating patients and families for their kind cooperation in this study. This work was supported by the Public Welfare Scientific Research Project of China (201402012) and the National Natural Science Foundation of China (81302598).

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Authors and Affiliations

  1. Research Center for Immunologic and Infectious diseases, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Tao Qin, Chaohong Liu, Rongxin Dai, Xiaohui Li, Liping Jiang & Xiaodong Zhao

  2. Division of Immunology; Research Center for Immunologic and Infectious Diseases; Ministry of Education Key Laboratory of Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Yunfei An, Junfeng Wu, Dawei Liu, Daoqi Wu, Xuemei Tang & Xiaodong Zhao

  3. Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA

    Wenxia Song

  4. Division of Immunology, Fujian Provincial Hospital, Fujian, 350001, China

    Tao Wang

  5. Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, 400014, China

    Xiaodong Zhao

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  1. Tao Qin
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  2. Yunfei An
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  12. Tao Wang
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Correspondence to Tao Wang or Xiaodong Zhao.

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All procedures performed in studies involving human materials were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Qin, T., An, Y., Liu, C. et al. Novel DOCK8 gene mutations lead to absence of protein expression in patients with hyper-IgE syndrome. Immunol Res 64, 260–271 (2016). https://doi.org/10.1007/s12026-015-8745-y

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  • DOI: https://doi.org/10.1007/s12026-015-8745-y

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